Mechanisms and Regulation of Neuronal Aging

 描述（由申请人提供）：神经系统对年龄的影响非常敏感。衰老以特定和有害的方式影响神经系统。老化的神经元修复损伤的能力较低，传递信息的能力较低，维持其正常形态的能力较低，并且更容易发生变性和神经退行性疾病。然而，尽管有明确的证据表明功能丧失，介导神经元老化的分子机制是模糊的。这个提议是针对神经元内的老化，也就是说，单个神经元如何对年龄做出反应，以及它们如何调节这种反应？同时，研究神经元老化可能影响整体寿命的方式。该项目特别关注随着年龄的增长，神经元修复受损轴突的能力急剧丧失，以及神经元老化的其他方面。初步数据确定了影响神经元老化的新的和特定的细胞生物学过程。该项目将阐明有助于神经元衰老的详细机制，测试它们的相互依赖性，并研究神经元衰老的不同功能方面是否受不同或共同机制的调节。每个目标都得到了广泛的初步数据，以及新的生物学概念和实验方法的支持。这些目标的完成将描述介导神经元老化的基本细胞机制，并有助于更全面地了解具有多种组织类型的复杂生物体的老化。

 DESCRIPTION (provided by applicant): The nervous system is highly susceptible to the effects of age. Aging affects the nervous system in specific and deleterious ways. Aging neurons are less able to repair injury, less able to transmit information, less able to maintain their normal morphology, and are more prone to degeneration and neurodegenerative disease. However, despite the clear evidence for functional loss, the molecular mechanisms that mediate neuronal aging are obscure. This proposal addresses aging within neurons-that is, how do individual neurons respond to age, and how do they regulate this response? At the same time, the ways in which neuronal aging may affect overall lifespan are investigated. The project focuses in particular on the dramatic loss of neuronal ability to repair damaged axons that occurs with age, as well as other aspects of neuronal aging. Preliminary data identify novel and specific cell-biological processes that affect neuronal aging. The project will elucidate the detailed mechanisms that contribute to neuronal aging, test their interdependence, and examine whether different functional aspects of neuronal aging are regulated by different or by common mechanisms. Each Aim is supported by extensive preliminary data, as well as by novel biological concepts and experimental approaches. Completion of these Aims will describe fundamental cellular mechanisms that mediate neuronal aging, and contribute to a more complete understanding of aging in complex organisms with multiple tissue types.